Osteoporosis, or bone loss, is a condition that accompanies aging as well as a variety of diseases of diverse etiology. These diseases include metabolic bone diseases, hypogonadism, hyperadrenocorticism, scurvy, heritable disorders of connective tissue such as osteogenesis imperfecta, homocystinuria, and Ehlers-Danlos syndrome, and other conditions such as rheumatoid arthritis and idiopathic osteoporosis. Age-related osteoporosis is particularly prevalent among post-menopausal women.
If detected early, osteoporosis can be treated by nutritional supplements, hormone replacement therapy, and certain prescription drugs. Unfortunately, osteoporosis is not readily identifiable by physical examination, and often remains undetected until a bone fracture occurs causing the individual to suffer pain, and possible deformity and disability. As one gets older, the ability to respond to these treatments diminishes, and the complications become more serious. Thus, early detection is an important means of lessening or preventing the consequences of osteoporosis, and improving the quality of life for those who are susceptible to this condition.
Osteoporosis is detectable by a variety of methods. These include x-ray absorptiometry by single-energy, dual-energy and peripheral means, radiographic absorptiometry, quantitative computed tomography, quantitative ultrasound, bone densitometry, and the chemical analysis of urine samples. The most convenient and cost-effective method is the chemical analysis of a urine sample to detect the levels of certain biochemical markers of bone turnover. The higher the rate of resorption relative to the rate of formation of bone tissue, the greater the rate of bone loss. The level of resorption in particular is readily determined on a quantitative basis by the analysis of urine for breakdown products of bone mineral and matrix. These breakdown products, or markers, are the collagen crosslinks pyridinoline and deoxypyridinoline, and the type I collagen breakdown products N-telopeptide and C-telopeptide.
Assays of urine for these markers is done by high-performance liquid chromatography (HPLC) and by immunoassays. These immunoassays can be performed on automated equipment for enhanced efficiency and to permit the analysis of large numbers of samples. As with any clinical analysis, quality control requires that precision and accuracy be maintained in the performance of the test and the analysis of the test results. For this reason, the use of control materials, which contain known amounts of the markers, is an important component of the laboratory protocol. Unfortunately, the isolation and purification of the markers from urine, either normal urine or urine having an elevated level of the markers, is a tedious and cumbersome process, and for this reason the controls for these markers are very expensive, and at times prohibitively so. A further disadvantage of controls prepared in this manner is that they are primarily buffer solutions in which the markers are dissolved, and buffer solutions differ substantially from the patient's urine sample. This affects the analytical procedures and detracts from the ability to make direct comparisons between the controls and the test samples.